Tracking Oregon's Progress: A Report of the Tracking Oregon's Progress (TOP) Indicators Project

In 1989, Oregon embarked on a novel experiment to track the progress of the state toward a set of economic, social and environmental goals embodied in the state strategic plan Oregon Shines. The task of tracking a set of indicators to measure progress was assigned to a new state entity: the Oregon Progress Board. For two decades, the Progress Board measured the state's progress using a set of social, economic and environmental indicators. After the 2009 report was completed however, the state decided not to continue funding the Progress Board and discontinued the tracking of state and county indicators.This 2014 report is a report to the people of Oregon. It identifies trends in the state that suggest both progress toward prosperity as well as issues that may be a source of future barriers and concerns. Like those who led previous indicator efforts, we hope that the report and website will be used by policymakers, government analysts, the press, business and civic leaders and the civically-engaged population to better understand the current social, economic, and environmental condition of the state

K-12 Student Success: Out-of-School time Initiative

This report is a summary of interim findings from the ongoing evaluation of the K-12 Student Success: Out-of-School Time Initiative

Combination of Isosorbide Dinitrate and Hydralazine in Blacks with Heart Failure

BACKGROUND We examined whether a fixed dose of both isosorbide dinitrate and hydralazine provides additional benefit in blacks with advanced heart failure, a subgroup previously noted to have a favorable response to this therapy. METHODS A total of 1050 black patients who had New York Heart Association class III or IV heart failure with dilated ventricles were randomly assigned to receive a fixed dose ofisosorbide dinitrate plus hydralazine or placebo in addition to standard therapy for heart failure. The primary end point was a composite score made up of weighted values for death from any cause, a first hospitalization for heart failure, and change in the quality of life. RESULTS The study was terminated early owing to a significantly higher mortality rate in the placebo group than in the group given isosorbide dinitrate plus hydralazine (10.2 percent vs. 6.2 percent, P=0.02). The mean primary composite score was significantly better in the group given isosorbide dinitrate plus hydralazine than in the placebo group (-0.1±1.9 vs. -0.5±2.0, P=0.01; range of possible values, -6 to + 2), as were its individual components (43 percent reduction in the rate of death from any cause [hazard ratio, 0.57; P=0.01] 33 percent relative reduction in the rate of first hospitalization for heart failure [16.4 percent vs. 22.4 percent, P=0.001], and an improvement in the quality of life [change in score, -5.6±20.6 vs. -2.7±21.2, with lower scores indicating better quality of life; P=0.02; range of possible values, 0 to 105]). CONCLUSIONS The addition ofa fixed dose of isosorbide dinitrate plus hydralazine to standard therapy for heart failure including neurohormonal blockers is efficacious and increases survival among black patients with advanced heart failure

Chromatin: a tunable spring at work inside chromosomes

This paper focuses on mechanical aspects of chromatin biological functioning. Within a basic geometric modeling of the chromatin assembly, we give for the first time the complete set of elastic constants (twist and bend persistence lengths, stretch modulus and twist-stretch coupling constant) of the so-called 30-nm chromatin fiber, in terms of DNA elastic properties and geometric properties of the fiber assembly. The computation naturally embeds the fiber within a current analytical model known as the ``extensible worm-like rope'', allowing a straightforward prediction of the force-extension curves. We show that these elastic constants are strongly sensitive to the linker length, up to 1 bp, or equivalently to its twist, and might locally reach very low values, yielding a highly flexible and extensible domain in the fiber. In particular, the twist-stretch coupling constant, reflecting the chirality of the chromatin fiber, exhibits steep variations and sign changes when the linker length is varied. We argue that this tunable elasticity might be a key feature for chromatin function, for instance in the initiation and regulation of transcription.Comment: 38 pages 15 figure

Influence of Blood Pressure on the Effectiveness of a Fixed-Dose Combination of Isosorbide Dinitrate and Hydralazine in the African-American Heart Failure Trial

OBJECTIVES: This study sought to assess the effect of baseline systolic blood pressure (SBP) and changes in SBP on the effectiveness of treatment with fixed-dose combination of isosorbide dinitrate and hydralazine (FDC I/H) in patients with heart failure (HF). BACKGROUND: Low SBP is a risk factor for adverse outcomes in patients with HF. However, FDC I/H lowered SBP in the A-HeFT (African-American Heart Failure Trial) and yet prolonged survival. Whether blood pressure (BP) lowering is critical to the efficacy of FDC I/H and whether a low BP limits its effectiveness is unclear. METHODS: The effects of FDC I/H on SBP and on mortality and hospitalization were compared in patients with a low or high baseline SBP using multivariable Cox regression models. The interaction between the effect of treatment and baseline SBP was examined. RESULTS: Mean +/- SD baseline SBP in all of the patients was 126 +/- 18 mm Hg. Patients with baseline SBP equal to or below the median (126 mm Hg) had features of more severe HF. Baseline SBP equal to or below the median was an independent risk factor for death (hazard ratio [HR] 2.09; 95% confidence interval [CI] 1.02 to 4.29) or first hospitalization for HF (HR 1.66; 95% CI 1.18 to 2.34). The FDC I/H treatment reduced BP in patients with SBP above the median but not in patients with SBP below 126 mm Hg. The FDC I/H treatment was associated with a similar decrease in mortality or hospitalization for HF in patients with SBP below the median and above the median. The effects of FDC I/H on mortality alone were also similar. CONCLUSIONS: In A-HeFT, patients with lower SBP had a greater risk but a similar relative benefit from the use of FDC I/H as those with higher SBP. The FDC I/H treatment did not reduce SBP in patients with low SBP. An asymptomatic low SBP should not be considered a contraindication to use of FDC I/H in patients with HF

Outcomes by Gender in the African-American Heart Failure Trial

OBJECTIVES Previous trials testing isosorbide dinitrate/hydralazine (I/H) were performed in all-male study cohorts, and thus the efficacy of I/H in women was unknown; 40% of the A-HeFT (African-American Heart Failure Trial) cohort were women. We therefore compared outcomes by gender and treatment. BACKGROUND Fixed-dose combined I/H significantly reduced mortality and heart failure hospitalizations and improved quality of life in 1,050 black patients with heart failure treated with background neurohormonal blockade. Previous trials testing I/H were done in all-male study cohorts, and thus the efficacy of I/H in women was unknown. METHODS Baseline characteristics and medications were compared between men and women by I/H and placebo treatment. Survival, time to first heart failure hospitalization, change in quality of life, and event-free survival were compared by gender and treatment. RESULTS At baseline, women had lower hemoglobin and creatinine levels; less renal insufficiency; and higher body mass indexes, diabetes prevalence, and systolic blood pressures; but worse quality of life scores. All-cause mortality was lower in women than in men treated with I/H but without significant treatment interaction by gender. The primary composite score, which weighted mortality, first heart failure hospitalization, and change in quality of life at 6 months, was similarly improved by I/H in men and women. First heart failure hospitalization and event-free survival (time to death or first heart failure hospitalization) were similarly improved in both genders. CONCLUSIONS Fixed-dose I/H improved heart failure outcomes in both men and women in A-HeFT. The I/H significantly improved the primary composite score and event-free survival as well as reduced the risk of first heart failure hospitalizations similarly in both genders. The I/H had a slightly greater mortality benefit in women, but without a significant treatment interaction by gender

How does FDAC succeed with parents with substance misuse problems?:Exploring relational practices within the English Family Drug Alcohol Court

Parental substance misuse is a significant risk factor for child maltreatment and is frequently involved in care proceedings. Outcomes are often poor and family reunification is prone to breakdown. In this article, the contribution of the English Family Drug and Alcohol Court (FDAC) is examined. Adapted from the US family drug treatment court model, FDAC offers a radically different approach to ordinary care proceedings by treating parents as well as adjudicating. The article draws on a mixed‐methods evaluation of FDAC which reports better recovery and reunification rates than ordinary court. It presents findings from interviews with 42 parents and 154 court observations of 89 cases, focusing on FDAC's relational practices. The article concludes that these relational practices offer hope to substance‐misusing parents and that the approach merits wider attention because of its therapeutic potential and distinctive approach to justice. Key Practitioner Messages FDAC is a helpful approach to care proceedings for substance‐misusing parents. Parents value clear, consistent and honest messages about their progress when delivered in the context of trusted relationships and intensive support. Parents need holistic help that takes into account damaging early‐life experiences

A model for Escherichia coli chromosome packaging supports transcription factor-induced DNA domain formation

What physical mechanism leads to organization of a highly condensed and confined circular chromosome? Computational modeling shows that confinement-induced organization is able to overcome the chromosome's propensity to mix by the formation of topological domains. The experimentally observed high precision of separate subcellular positioning of loci (located on different chromosomal domains) in Escherichia coli naturally emerges as a result of entropic demixing of such chromosomal loops. We propose one possible mechanism for organizing these domains: regulatory control defined by the underlying E. coli gene regulatory network requires the colocalization of transcription factor genes and target genes. Investigating this assumption, we find the DNA chain to self-organize into several topologically distinguishable domains where the interplay between the entropic repulsion of chromosomal loops and their compression due to the confining geometry induces an effective nucleoid filament-type of structure. Thus, we propose that the physical structure of the chromosome is a direct result of regulatory interactions. To reproduce the observed precise ordering of the chromosome, we estimate that the domain sizes are distributed between 10 and 700 kb, in agreement with the size of topological domains identified in the context of DNA supercoiling

An All-Atom Model of the Chromatin Fiber Containing Linker Histones Reveals a Versatile Structure Tuned by the Nucleosomal Repeat Length

In the nucleus of eukaryotic cells, histone proteins organize the linear genome into a functional and hierarchical architecture. In this paper, we use the crystal structures of the nucleosome core particle, B-DNA and the globular domain of H5 linker histone to build the first all-atom model of compact chromatin fibers. In this 3D jigsaw puzzle, DNA bending is achieved by solving an inverse kinematics problem. Our model is based on recent electron microscopy measurements of reconstituted fiber dimensions. Strikingly, we find that the chromatin fiber containing linker histones is a polymorphic structure. We show that different fiber conformations are obtained by tuning the linker histone orientation at the nucleosomes entry/exit according to the nucleosomal repeat length. We propose that the observed in vivo quantization of nucleosomal repeat length could reflect nature's ability to use the DNA molecule's helical geometry in order to give chromatin versatile topological and mechanical properties